ArticleCell death & disease2016
A HIF-1α-driven feed-forward loop augments HIF signalling in Hep3B cells by upregulation of ARNT.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- A dynamic model of gene activation in response to hypoxia accounting for both HIF-1 and HIF-2.Briefings in functional genomics · 2025Article
- Targeting the hypoxia signaling pathway with nanomedicine to reverse immunotherapy resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- The astrocyte-produced growth factor HB-EGF limits autoimmune CNS pathology.Nature immunology · 2024Article
- Article
- Genetic variants in hypoxia-inducible factor pathway are associated with colorectal cancer risk and immune infiltration.Journal of cellular and molecular medicine · 2024Article
- Hypoxic Effects on Matrix Metalloproteinases' Expression in the Tumor Microenvironment and Therapeutic Perspectives.International journal of molecular sciences · 2023Review
- Conditional Deletion of HIF-2α in Mouse Nucleus Pulposus Reduces Fibrosis and Provides Mild and Transient Protection From Age-Dependent Structural Changes in Intervertebral Disc.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- The circadian transcription factor ARNTL2 is regulated by weight-loss interventions in human white adipose tissue and inhibits adipogenesis.Cell death discovery · 2022Article
- Recent Developments in the Study of the Microenvironment of Cancer and Drug Delivery.Current drug metabolism · 2022Article
- Oxygen-sensing mechanisms in development and tissue repair.Development (Cambridge, England) · 2021Review
- Profound changes in cerebrospinal fluid proteome and metabolic profile are associated with congenital hydrocephalus.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Article
- Hypoxia-Induced Non-Coding RNAs Controlling Cell Viability in Cancer.International journal of molecular sciences · 2021Review
- Reprogramming of Mesothelial-Mesenchymal Transition in Chronic Peritoneal Diseases by Estrogen Receptor Modulation and TGF-β1 Inhibition.International journal of molecular sciences · 2020Review
- Meloxicam, a Selective COX-2 Inhibitor, Mediates Hypoxia-Inducible Factor- (HIF-) 1Oxidative medicine and cellular longevity · 2020Article
- Chemoprevention of Colorectal Cancer by Anthocyanidins and Mitigation of Metabolic Shifts Induced by Dysbiosis of the Gut Microbiome.Cancer prevention research (Philadelphia, Pa.) · 2020Article
- Upregulation of aryl hydrocarbon receptor nuclear translocator 2 in the hippocampi of post-stroke depression rats.Biomedical reports · 2019Article
- Changes in chromatin state reveal ARNT2 at a node of a tumorigenic transcription factor signature driving glioblastoma cell aggressiveness.Acta neuropathologica · 2018Article
- The hypoxic tumour microenvironment.Oncogenesis · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxygen-deprived (hypoxic) areas are commonly found within neoplasms caused by excessive cell proliferation. The transcription factor Aryl hydrocarbon receptor nuclear translocator (ARNT) is part of the hypoxia-inducible factor (HIF) pathway, which mediates adaptive responses to ensure cellular survival under hypoxic conditions. HIF signalling leads to metabolic alterations, invasion/metastasis and the induction of angiogenesis in addition to radio-chemoresistance of tumour cells. Activation of the HIF pathway is based on the abundance of HIF-α subunits, which are regulated in an oxygen-dependent manner and form transcriptional active complexes with ARNT or ARNT2 (also referred as HIF-1β and HIF-2β, respectively). ARNT is considered to be unaffected by hypoxia but certain cell lines, including Hep3B cells, are capable to elevate this transcription factor in response to oxygen deprivation, which implies an advantage. Therefore, the aim of this study was to elucidate the mechanism of hypoxia-dependent ARNT upregulation and to determine implications on HIF signalling. Gene silencing and overexpression techniques were used to alter the expression pattern of HIF transcription factors under normoxic and hypoxic conditions. qRT-PCR and western blotting were performed to measure gene and protein expression, respectively. HIF activity was determined by reporter gene assays. The results revealed a HIF-1α-dependent mechanism leading to ARNT upregulation in hypoxia. Forced expression of ARNT increased reporter activity under normoxic and hypoxic conditions. In conclusion, these findings indicate a novel feed-forward loop and suggest that ARNT might be a limiting factor. Augmented HIF signalling in terms of elevated target gene expression might be advantageous for tumour cells.
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